Chromosome abnormalities are often associated with genetic disorders, degenerative diseases, and cancer. The deletion or multiplication of copies of whole chromosomes and the deletion or amplifications of chromosomal segments or specific regions are common occurrences in cancer (Smith (1991) Breast Cancer Res. Treat. 18: Suppl. 1:5-14; van de Vijer (1991) Biochim. Biophys. Acta. 1072:33-50). In fact, amplifications and deletions of DNA sequences can be the cause of a cancer. For example, proto-oncogenes and tumor-suppressor genes, respectively, are frequently characteristic of tumorigenesis (Dutrillaux (1990) Cancer Genet. Cytogenet. 49: 203-217). Clearly, the identification and cloning of specific genomic regions associated with cancer is crucial both to the study of tumorigenesis and in developing better means of diagnosis and prognosis.
One of the amplified regions found in studies of breast and colon cancer cells is on chromosome 20, specifically, 20q13.2 (see, e.g. WO98/02539). Amplification of 20q13.2 was subsequently found to occur in a variety of tumor types and to be associated with aggressive tumor behavior. Increased 20q13.2 copy number has been found in 40% of breast cancer cell lines and 18% of primary breast tumors (Kalliioniemi (1994) Proc. Natl. Acad. Sci. USA 91: 2156-2160). Copy number gains at 20q13.2 have also been reported in greater than 25% of cancers of the ovary (Iwabuchi (1995) Cancer Res. 55:6172-6180), colon (Schlegel (1995) Cancer Res. 55: 6002-6005 and WO02/06526), head-and-neck (Bockmuhl (1996) Laryngor. 75: 408-414), brain (Mohapatra (1995) Genes Chromosomes Cancer 13: 86-93), pancreas (Solinas-Toldo (1996) Genes Chromosomes Cancer 20:399-407).
A number of studies have elucidated genetic alterations that occur during the development of colorectal tumors. For instance, deletions of p53 genes on chromosome 17p are often late events associated with the transition from the benign (adenoma) to the malignant (carcinoma) state. See Vogelstein et al., New England Journal of Medicine, 319:525 (1988), Fearon and Vogelstein, Cell, 61:759-767 (1990) and Baker et al. Cancer Res. 50:7717-22 (1990). More recently, comparative genomic hybridization has shown that specific patterns of chromosomal gains and losses take place during colorectal carcinogenesis (see, e.g. Schlegel, et al. Cancer Research. 55, 6002-6005 (1995); Ried, et al. Genes, Chromosomes & Cancer 15, 234-245 (1996); and Nakao et al., Jpn. J. Surg. 28, 567-569 (1998). These changes included overrepresentation (amplification) of large portion of chromosome 20 material.
The identification of new genes that are responsible for carcinogenesis is obviously great use in diagnosis, prognosis and treatment of these diseases. The present invention addresses these and other needs.